Posaconazole-glutaric acid cocrystal tablet with improved Dissolution rate

Abstract

Posaconazole is used to prevent fungal infections in patients having severely weakened immune system and has poor aqueous solubility which impairs its dissolution in upper gastric fluid producing problems in different formulations. These characteristics hinder its therapeutic application by delaying absorption rate and thereby onset of action. In the present study, an attempt was made to prepare posaconazole cocrystals with improved physicochemical properties for better therapeutic activity. Cocrystals were prepared with glutaric acid in 1:1 molar using ethanol by solvent drop grinding technique. The co-crystals formed were characterized by melting point determination, fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and dissolution studies. Posaconazole-glutaric acid co-crystals were further formulated as fast disintegrating tablets. The IR study revealed the shifting of characteristic bands of posaconazole. The PXRD pattern indicated cocrystal crystallinity and a considerable difference in 2θ value of intense peaks. The variation in fusion endotherm, which is in agreement with melting point, was designated by DSC spectra of posaconazole cocrystal. A significant improvement in the dissolution rate was observed in the case of cocrystals based tablets than pure posaconazole tablets.